Serum Extracellular Vesicle Protein Profiling for Prediction of Corneal Transplant Rejection.

BACKGROUND: Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival. METHODS: In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation. RESULTS: Our time course study revealed a decrease in the number of serum EVs on day 1, followed by a gradual increase by day 7. A comparative analysis of proteomics profiles of EVs from transplant recipients with rejection (rejectors) and without rejection (nonrejectors) found a distinct enrichment of histocompatibility 2, Q region locus 2, which is a part of major histocompatibility complex-class I of donor C57BL/6 mice, in day 7 EVs of rejectors, compared with nonrejectors, syngeneic controls, or naïve mice. In contrast, serum amyloid A2, a protein induced in response to injury, was increased in day 7 EVs of nonrejectors. CONCLUSIONS: Our findings offer noninvasive EV-based potential biomarkers for predicting corneal allograft rejection or tolerance.

Perceived Discrimination as a Critical Factor Affecting Self-Esteem, Satisfaction with Physical Appearance and Depression of Racial/Ethnic Minority Adolescents in Korea.

The effect of perceived discrimination on adolescents' developmental outcome has long been a topic of research, however, little is known about how it affects their depression especially among the racial/ethnic minority adolescents in Asian countries. In Korea, a country with a relatively short history of immigrant influx, discrimination has become an important social issue affecting a rapidly growing population. This study examines the impact of perceived discrimination on racial/ethnic minority adolescents in Korea, specifically focusing on its impact on depression through self-esteem and satisfaction with physical appearance. The Multicultural Adolescents Panel Study data were used for analyses, and the SPSS Process Macro program was used to test the parallel mediating effects of self-esteem and satisfaction with physical appearance. The findings show that perceived discrimination was a strong predictor of their depression. Self-esteem and satisfaction with physical appearance also had significant mediating effect. There were no distinct gender differences among paths though the male adolescents were found to have more discriminatory experiences than the female adolescents. The findings call for the development of healthy coping strategies for these adolescents to prevent the effect of perceived discrimination, not only for their mental health, but also with their self-perception including physical appearance.

Scytosiphon lomentaria Extract Ameliorates Obesity and Modulates Gut Microbiota in High-Fat-Diet-Fed Mice.

Scytosiphon lomentaria (SL) is a brown seaweed with antioxidant and anti-inflammatory properties; however, its effects on obesity are unknown. In this research, we investigated the anti-obesity properties and underlying mechanisms of the SL extract in vitro and in vivo. In 3T3-L1 preadipocytes, SL extract inhibited lipid accumulation, decreased the expression of Acc1, C/ebpa, Pparg mRNA and p-ACC1, and increased the expression of Ucp1 mRNA, UCP1 and p-AMPK. In animal experiments, mice were fed a chow diet, a high-fat diet (HF; 60% of calories as fat), and high-fat diet with SL extract (150 and 300 mg/kg body weight) for eight weeks (n = 10/group). SL extract reduced HF-induced weight gain, epididymal fat weight, fat cell size, LDL-C, leptin, fasting glucose, and glucose tolerance. In addition, SL extract had comparable effects on mRNA expression in WAT and liver to those observed in vitro, thereby inhibiting p-ACC1/ACC1 and increasing p-AMPK/AMPK and UCP1 expression. Furthermore, SL extract decreased HF-induced Firmicutes/Bacteroidetes ratio and reversed HF-reduced Bacteroides spp., Bacteroides vulgatus, and Faecalibacterium prausnitzii. These findings suggest that SL extract can aid in weight loss in mice fed a high-fat diet by altering adipogenic and thermogenic pathways, as well as gut microbiota composition.

Sargassum thunbergii Extract Attenuates High-Fat Diet-Induced Obesity in Mice by Modulating AMPK Activation and the Gut Microbiota.

Sargassum thunbergii (Mertens ex Roth) Kuntze (ST) is a brown alga rich in indole-2-carboxaldehyde. This study aimed to investigate the anti-obesity effects of ethanol extract from ST in in vitro and in vivo models. In 3T3-L1 cells, ST extract significantly inhibited lipid accumulation in mature adipocytes while lowering adipogenic genes (C/epba and Pparg) and enhancing metabolic sensors (Ampk, Sirt1), thermogenic genes (Pgc-1a, Ucp1), and proteins (p-AMPK/AMPK and UCP1). During animal investigation, mice were administered a chow diet, a high-fat diet (HF), or an HF diet supplemented with ST extract (at dosages of 150 and 300 mg/kg bw per day) for 8 weeks (n = 10/group). ST extract administration decreased weight gain, white adipose tissue weight, LDL-cholesterol, and serum leptin levels while improving glucose intolerance. In addition, ST extract increased the expression of Ampk and Sirt1 in adipose tissue and in the liver, as well as p-AMPK/AMPK ratio in the liver, compared to HF-fed mice. The abundance of Bacteroides vulgatus and Faecalibacterium prausnitzii in the feces increased in response to ST extract administration, although levels of Romboutsia ilealis decreased compared with those in HF-fed mice. ST extract could prevent obesity in HF-fed mice via the modulation of AMPK activation and gut microbiota composition.

Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia.

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

MHC Class I Enables MSCs to Evade NK-Cell-Mediated Cytotoxicity and Exert Immunosuppressive Activity.

Allogeneic mesenchymal stem/stromal cells (MSCs) are frequently used in clinical trials due to their low expression of major histocompatibility complex (MHC) class I and lack of MHC class II. However, the levels of MHC classes I and II in MSCs are increased by inflammatory stimuli, raising concerns over potential adverse effects associated with allogeneic cell therapy. Also, it is unclear how the host immune response to MHC-mismatched MSCs affects the therapeutic efficacy of the cells. Herein, using strategies to manipulate MHC genes in human bone marrow-derived MSCs via the CRISPR-Cas9 system, plasmids, or siRNAs, we found that inhibition of MHC class I-not MHC class II-in MSCs lowered the survival rate of MSCs and their immunosuppressive potency in mice with experimental autoimmune uveoretinitis, specifically by increasing MSC vulnerability to natural killer (NK)-cell-mediated cytotoxicity. A subsequent survey of MSC batches derived from 6 human donors confirmed a significant correlation between MSC survival rate and susceptibility to NK cells with the potency of MSCs to increase MHC class I level upon stimulation. Our overall results demonstrate that MHC class I enables MSCs to evade NK-cell-mediated cytotoxicity and exert immunosuppressive activity.

In vitro digestion, absorption and biological activities of acylated anthocyanins from purple sweet potatoes (Ipomoea batatas).

Purple sweet potatoes (PSP) are widely used as color enhancers in food formulations. Investigations on the stability of PSP polyphenolics during simulated digestion and subsequent absorption in a Caco-2 cell monolayer model were accomplished. Measures of bioactive activities were also assessed in vitro. PSP whole polyphenolic extracts as a control (WC) were compared to isolates enriched in anthocyanins (AC) or non-anthocyanin phenolics (NAP). Anthocyanins were also alkali-hydrolyzed to remove acylated moieties. Compounds were subjected to simulated gastro-intestinal digestions where non-hydrolyzed anthocyanins showed higher stability compared to alkali-hydrolyzed. For many alkali-hydrolyzed anthocyanins, the transport through a Caco-2 cell monolayer was reduced. PSP fractions significantly increased the generation of reactive oxygen species in HT-29 cells and was suppressive in the CCD-18Co cells while down-regulated mRNA expression of inflammatory markers. Results indicate the importance of PSP composition and the effects of acyl moieties on anthocyanin stability and functional properties for food colors.

Identification of Molecules Responsible for Therapeutic Effects of Extracellular Vesicles Produced from iPSC-Derived MSCs on Sjo¨gren's Syndrome.

Recent research indicated that extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) are a promising alternative to MSCs for immunomodulatory therapy. However, the contents of MSC-EVs would change as their parent MSCs change, hence the therapeutic efficacy of MSC-derived EVs (MSC-EVs) would largely depend on donors, tissue sources and culture conditions of MSCs. To overcome limitations of tissue-derived MSCs, we previously used MSCs derived from human induced pluripotent stem cells (iMSCs) to produce EVs and demonstrated their therapeutic potential in a mouse model of secondary Sjo¨gren's Syndrome. Here, we further found that EVs from early-passage iMSCs had better immunomodulatory potency than EVs from late-passage iMSCs in TLR4-stimulated splenocytes and in a mouse model of primary Sjögren's syndrome. Comparative molecular profiling using proteomics and microRNA sequencing revealed distinctive molecular profiles of iMSC-EVs with or without immunomodulation capacity. Amongst them, manipulation of TGF-ß1, miR-21 and miR-125b levels in iMSC-EVs significantly affected their immunosuppressive effects. These findings would help improve our understanding of the molecular mechanism underlying iMSC-EV-mediated immunomodulation and further provide strategies to improve regulatory function of EVs for the treatment of immune-mediated diseases.

A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers.

Human mesenchymal stem cells (hMSCs) are effective in treating disorders resulting from an inflammatory or heightened immune response. The hMSCs derived from induced pluripotent stem cells (ihMSCs) share the characteristics of tissue derived hMSCs but lack challenges associated with limited tissue sources and donor variation. To meet the expected future demand for ihMSCs, there is a need to develop scalable methods for their production at clinical yields while retaining immunomodulatory efficacy. Herein, we describe a platform for the scalable expansion and rapid harvest of ihMSCs with robust immunomodulatory activity using degradable gelatin methacryloyl (GelMA) microcarriers. GelMA microcarriers were rapidly and reproducibly fabricated using a custom microfluidic step emulsification device at relatively low cost. Using vertical wheel bioreactors, 8.8 to 16.3-fold expansion of ihMSCs was achieved over 8 days. Complete recovery by 5-minute digestion of the microcarriers with standard cell dissociation reagents resulted in >95% viability. The ihMSCs matched or exceeded immunomodulatory potential in vitro when compared with ihMSCs expanded on monolayers. This is the first description of a robust, scalable, and cost-effective method for generation of immunomodulatory ihMSCs, representing a significant contribution to their translational potential.

Mango (Mangifera indica L.) Polyphenols: Anti-Inflammatory Intestinal Microbial Health Benefits, and Associated Mechanisms of Actions.

Mango is rich in polyphenols including gallotannins and gallic acid, among others. The bioavailability of mango polyphenols, especially polymeric gallotannins, is largely dependent on the intestinal microbiota, where the generation of absorbable metabolites depends on microbial enzymes. Mango polyphenols can favorably modulate bacteria associated with the production of bioactive gallotannin metabolites including Lactobacillus plantarum, resulting in intestinal health benefits. In several studies, the prebiotic effects of mango polyphenols and dietary fiber, their potential contribution to lower intestinal inflammation and promotion of intestinal integrity have been demonstrated. Additionally, polyphenols occurring in mango have some potential to interact with intestinal and less likely with hepatic enzymes or transporter systems. This review provides an overview of interactions of mango polyphenols with the intestinal microbiome, associated health benefits and underlying mechanisms.

10-Year Trends of Emergency Department Visits, Wait Time, and Length of Stay among Adults with Mental Health and Substance use Disorders in the United States.

This study examined if there was a change in the number of Emergency Department (ED) visits, wait time, and length of stay among adults with mental health and substance use disorders (MHSUD) in the United States from 2006 to 2015. From the National Hospital Ambulatory Medical Care Survey, a total of 17,488 ED visits by adults with MHSUD were identified. Linear regression and negative binomial regression analyses were conducted to assess statistically significant changes in trends of ED visits, wait time, and length of stay. Results indicated that ED visits by adults with MHSUD increased by 30.6% from 2006 to 2015. Wait time of ED visits by adults with MHSUD decreased for the same time period; however, length of stay did not change. Also, there were some differences in trends of wait time and length of stay by diagnosis. Specifically, wait time of ED visits by adults with psychotic disorders did not decrease. Length of stay of ED visits by adults with anxiety disorders statistically significantly increased from 2006 to 2015. More effort is needed to improve the quality of ED care for adults with MHSUD. In such an effort, diagnoses should be taken into consideration.

Comprehensive Molecular Profiles of Functionally Effective MSC-Derived Extracellular Vesicles in Immunomodulation.

Accumulating evidence indicates that mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) exhibit immunomodulatory effects by delivering therapeutic RNAs and proteins; however, the molecular mechanism underlying the EV-mediated immunomodulation is not fully understood. In this study, we found that EVs from early-passage MSCs had better immunomodulatory potency than did EVs from late-passage MSCs in T cell receptor (TCR)- or Toll-like receptor 4 (TLR4)-stimulated splenocytes and in mice with ocular Sjögren's syndrome. Moreover, MSC-EVs were more effective when produced from 3D culture of the cells than from the conventional 2D culture. Comparative molecular profiling using proteomics and microRNA sequencing revealed the enriched factors in MSC-EVs that were functionally effective in immunomodulation. Among them, manipulation of transforming growth factor ß1 (TGF-ß1), pentraxin 3 (PTX3), let-7b-5p, or miR-21-5p levels in MSCs significantly affected the immunosuppressive effects of their EVs. Furthermore, there was a strong correlation between the expression levels of TGF-ß1, PTX3, let-7b-5p, or miR-21-5p in MSC-EVs and their suppressive function. Therefore, our comparative strategy identified TGF-ß1, PTX3, let-7b-5p, or miR-21-5p as key molecules mediating the therapeutic effects of MSC-EVs in autoimmune disease. These findings would help understand the molecular mechanism underlying EV-mediated immunomodulation and provide functional biomarkers of EVs for the development of robust EV-based therapies.

How Do Time Use and Social Relationships Affect the Life Satisfaction Trajectory of Korean Adolescents?

This study investigated the life satisfaction trajectory of Korean adolescents, and factors associated with changes in life satisfaction. Specifically, we focused on how changes in time use and social relationships were associated with changes in life satisfaction. Using three waves of the Korean Children and Youth Panel Survey, we conducted a series of multilevel growth curve modeling analyses. The results indicate that Korean adolescents' life satisfaction decreased over a three-year period, and that time spent on leisure and sleeping were both significant predictors of changes in life satisfaction. Life satisfaction decreased at a slower rate for adolescents whose relationships with peers and teachers positively increased over time. Findings highlight the importance of ensuring adequate amount of sleep and providing various opportunities for leisure activities in improving Korean adolescents' life satisfaction. Furthermore, social relationships, specifically with teachers and peers should be the focus of prevention and intervention for adolescents to maintain and improve their level of life satisfaction.

Mango (Mangifera indica L.) polyphenols reduce IL-8, GRO, and GM-SCF plasma levels and increase Lactobacillus species in a pilot study in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) characterized by chronic intestinal inflammation and intestinal microbial dysbiosis present a major risk factor in the development of colorectal cancer. Previously, dietary polyphenols from mango (Mangifera indica L.) such as gallotannins and gallic acid have been shown to mitigate intestinal inflammation and carcinogenesis, as well as modulate intestinal microbial composition. To further translate findings from preclinical models, we hypothesized that mango polyphenols possess anti-inflammatory and microbiome-modulatory activities and may improve symptoms of IBD, reduce biomarkers for inflammation and modulate the intestinal microbiome when administered as an adjuvant treatment in combination with conventional medications in patients with mild to moderate IBD. In this study, ten participants received a daily dose of 200-400 g of mango pulp for 8 weeks (NCT02227602). Mango intake significantly improved the primary outcome Simple Clinical Colitis Activity Index (SCCAI) score and decreased the plasma levels of pro-inflammatory cytokines including interleukin-8 (IL-8), growth-regulated oncogene (GRO) and granulocyte macrophage colony-stimulating factor (GM-CSF) by 16.2% (P = .0475), 25.0% (P = .0375) and 28.6% (P = .0485), all factors related to neutrophil-induced inflammation, respectively. Mango intake beneficially altered fecal microbial composition by significantly increasing the abundance of Lactobacillus spp., Lactobacillus plantarum, Lactobacillus reuteri and Lactobacillus lactis, which was accompanied by increased fecal butyric acid production. Therefore, enriching diet with mango fruits or potentially other gallotannin-rich foods seems to be a promising adjuvant therapy combined with conventional medications in the management of IBD via reducing biomarkers of inflammation and modulating the intestinal microbiota.

Improved recovery of galloyl metabolites from mango (Mangifera indica L.) in human plasma using protein precipitation with sodium dodecyl sulfate and methanol.

Extraction of polyphenolic metabolites from blood fractions can be challenging since compound recovery can be limited by chemical structure, polarity, and protein-binding affinity of analytes. Gallic acid and its metabolites exhibit particularly low recoveries from plasma and can lead to an underestimation of their bioavailability from foods. A modified method to extract free gallic acid and its metabolites from human plasma aided by sodium dodecyl sulfate and acidified methanol (SDS-MeOH) was applied to extract free gallic acid and its metabolites from human plasma after a single consumption of 400 g of mango (cv. Ataulfo) pulp by 10 healthy male and female subjects. The use of SDS-MeOH facilitated extraction of significantly (p < 0.05) more pyrogallol, free gallic acid, 4-O-methylgallic acid, and ethyl gallate with recovery rates exceeding 80% in standard recovery from human blood plasma when compared to conventional methods that rely on solvent extraction or solid phase extraction. The method was reproducible and precise for standards from 50 to 500 µg/L. In pharmacokinetic plasma samples five predominant metabolites of gallic acid were tentatively characterized by HPLC-MS and absorption kinetics evaluated over 8 h for catechol-O-sulfate, 4-O-methylgallic acid-3-O-sulfate, and pyrogallol-O-sulfate, methylpyrogallol-O-sulfate, and 4-O-methylgallic acid with AUC0-8h of 9520 ± 3370, 6030 ± 1310, 5990 ± 1690, 4020 ± 1040, and 2790 ± 1190 µg/L h respectively. Plasma extraction was rapid and reproducible with superior recovery rates compared to conventional methods when evaluating polar phenolic metabolites.

Gallotannins and Lactobacillus plantarum WCFS1 Mitigate High-Fat Diet-Induced Inflammation and Induce Biomarkers for Thermogenesis in Adipose Tissue in Gnotobiotic Mice.

SCOPE: Intestinal microbial metabolites from gallotannins (GT), including gallic acid (GA) and pyrogallol (PG), may possess potential anti-obesogenic properties. Lactobacillus plantarum (L. plantarum) found in the intestinal microbiome encodes for enzymatic activities that metabolize GT into GA and PG. Anti-obesogenic activities of orally administered GT in the presence or absence of L. plantarum is examined in gnotobiotic mice fed a high-fat diet (HFD). METHODS AND RESULTS: Germ-free (GF) C57BL/6J mice are divided into three groups, GF control, GF gavaged with GT, and mice colonized with L. plantarum and gavaged with GT. Compared to the control, GT decreases the expressions of lipogenic genes (e.g., fatty acid synthase (FAS)) in epididymal white adipose tissue and increases thermogenic genes (e.g., nuclear factor erythroid-2-like 1 (Nfe2l1)) in interscapular brown adipose tissue. Intestinal colonization with L. plantarum enhances these effects, and mice colonized with L. plantarum exhibit lower levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), leptin and plasma insulin. CONCLUSIONS: Results indicate that GT and L. plantarum reduce HFD-induced inflammation, insulin resistance, and promote thermogenesis in adipose tissue potentially through the activity of GT-metabolizing bacterial enzymes yielding absorbable bioactive GT metabolites. These findings imply the potential role of prebiotic-probiotic interactions in the prevention of diet-induced metabolic disorders.

Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model.

Predominant flavonoids in cereals and pulses are structurally different and may positively interact to enhance bioactivity in combined diet. This work investigated the effects of combined cereal 3-deoxyflavonoids (apigenin, naringenin) and pulse flavonols (quercetin), along with natural extracts, on their bioavailability and underlying mechanisms using Caco-2 monolayer model. Membrane permeability, phase II metabolism, and ATP binding cassette (ABC) membrane transporter expression and function were measured. Apparent absorption of quercetin and apigenin increased (p < 0.05) 3.3× and 1.5×, respectively, while both compounds were significantly less metabolized in combined treatments. Combinations with naringenin had insignificant effect, suggesting a role for flavonoid C2C3 conjugation. Both natural extracts and apigenin-quercetin combinations synergistically (3-40 fold) downregulated ABC transporter expression, and inhibited P-glycoprotein activity, suggesting direct binding and inhibition of ATPase. Combination of conjugated cereal and pulse flavonoids enhances their potential bioavailability through synergistic inhibition of membrane transporter and phase II enzyme function.

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6-Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals.

SCOPE: This human clinical pilot trial investigated pharmacokinetics of gallotannin-metabolites and modulation of intestinal microbiota in healthy lean and obese individuals after 6 weeks of daily mango consumption. METHODS AND RESULTS: Participants are divided into three groups: Lean Mango (LM: n = 12; BMI = 22.9 kg m-2 ), Obese Mango (OM: n = 9; BMI = 34.6 kg m-2 ), and Lean Control (LC: n = 11; BMI = 22.1 kg m-2 ). LM and OM consumed 400 g of mango per day for 6 weeks. LC consumed mango only on Days 0 and 42. After 6 weeks, LM experienced increased systemic exposure (AUC0-8h ) to gallotannin-metabolites, 1.4-fold (p = 0.043). The greatest increase is 4-O-methyl-gallic acid, 3.3-fold (p = 0.0026). Cumulative urinary excretion of gallotannin-metabolites significantly increased in LM and OM, but not LC. For OM, qPCR data show increased levels of tannase-producing Lactococcus lactis and decreased levels of Clostridium leptum and Bacteroides thetaiotaomicron, bacteria associated with obesity. LM experienced an increased trend of fecal levels of butyric (1.3-fold; p = 0.09) and valeric acids (1.5-fold; p = 0.056). Plasma endotoxins showed a decreased trend in LM and OM. CONCLUSION: Continuous mango intake significantly increased systemic exposure to gallotannin- metabolites and induced an increased trend for fecal short-chain fatty acids in lean but not obese individuals. This pharmacokinetic discrepancy may result in BMI-associated reduced gallotannin-derived health benefits.

Açaí (Euterpe oleracea Mart.) beverage consumption improves biomarkers for inflammation but not glucose- or lipid-metabolism in individuals with metabolic syndrome in a randomized, double-blinded, placebo-controlled clinical trial.

Açaí (Euterpe oleracea Mart.) berries, characterized by high polyphenol concentrations (predominantly anthocyanins), have demonstrated anti-inflammatory and anti-diabetic activities. The study objective was to determine the modulation of lipid and glucose-metabolism, as well as oxidative stress and inflammation, by an açaí-beverage (containing 1139 mg L-1 gallic acid equivalents of total polyphenolics) in 37 individuals with metabolic syndrome (BMI 33.5 ± 6.7 kg m-2) who were randomized to consume 325 mL twice per d of a placebo control or açaí-beverage for 12 weeks. Anthropometric measurements, dietary intake, and blood and urine samples were collected at baseline and after 12 weeks of consumption. Two functional biomarkers, plasma level of interferon gamma (IFN-γ) and urinary level of 8-isoprostane, were significantly decreased after 12 weeks of açaí consumption compared to the placebo control (p = 0.0141 and 0.0099, respectively). No significant modification of biomarkers for lipid- and glucose-metabolism was observed in this study. Findings from this small pilot study provide a weak indication that the selected dose of açaí polyphenols may be beneficial in metabolic syndrome as only two biomarkers for inflammation and oxidative stress were improved over 12 weeks. Follow-up studies should be conducted with higher polyphenol-doses before drawing conclusions regarding the efficacy of açaí polyphenols in metabolic syndrome.

Obesity-Associated Diseases Biomarkers Are Differently Modulated in Lean and Obese Individuals and Inversely Correlated to Plasma Polyphenolic Metabolites After 6 Weeks of Mango (Mangifera indica L.) Consumption.

SCOPE: Mangos are a rich source of gallotannin-derived polyphenols that may exert anti-inflammatory effects relevant to obesity-related chronic diseases. This randomized human clinical study investigated the influence of daily mango supplementation for 6 weeks on inflammation and metabolic functions in lean and obese individuals. METHODS AND RESULTS: Lean (n = 12, body mass index [BMI] 18-26.2 kg m-2 ) and obese (n = 9, BMI >28.9 kg m-2 ) participants, aged 18-65 years received daily 400 g of mango pulp for 6 weeks. Inflammatory cytokines, metabolic hormones, and lipid profiles were examined in plasma before and after 6 weeks. In lean participants, systolic blood pressure was lowered by 4 mmHg after 6 weeks. In obese participants, hemoglobin A1c (HbA1c) and plasminogen activator inhibitor-1 (PAI-1) were reduced by 18% and 20%, respectively. Obese participants showed decreased plasma concentrations (area under the curve [AUC] 0-8h ) of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1). Correlation analysis indicates that the beneficial effects of mango supplementation on pro-inflammatory cytokines, PAI-1 and HbA1c, are associated with systemic exposure to polyphenolic metabolites. CONCLUSIONS: Mango supplementation improves the plasma levels of pro-inflammatory cytokines and metabolic hormones in obese participants. There is a crucial need to investigate the role of lowered polyphenolic absorption in obese individuals on their efficacy in reducing biomarkers for inflammation and other risk factors for chronic diseases.